The present invention relates to a process of producing inorganic compositions suitable as carriers for pharmaceutically active compounds to be administered to human beings or to any other mammal.
Calcium sulphate is used for a variety of purposes and exists in various forms and states of hydration.
The calcium sulphate hydrates, in particular gypsum (calcium sulphate dihydrate) and the hemi-hydrate, are used in a number of industrial applications for a wide range of purposes, e.g. as an additive for the production of cements, gypsum wallboards, or bone void fillers for orthopaedic and dental applications. Some of these void filler products also contain an active pharmaceutical ingredients whereby a slow release pharmaceutical composition is achieved. In the form of γ-anhydrite (the anhydrous form), calcium sulphate is used as a desiccant.
Calcium sulphate hemihydrate exists in at least two distinct morphological forms, denoted α and β. The preparation route is of crucial importance for which of the two forms that is obtained. Christensen et al in Dalton Trans., 2010, 39, 2044-2048 suggests that the α-form can be obtained at hydrothermal conditions, i.e. temperature range of 120 to 160° C. and at pressures up to 8 bar, while the β-form can be obtained by dry heating in the temperature range 120 to 180° C. At temperatures above 170° C. γ-anhydrite may begin to form, Christensen et al, Chem. Mater. 2008, 20, 2124-2132.
It has been found that the method of manufacturing the calcium sulphate hemihydrate is essential for the dissolution characteristics of a formulation prepared by the hemihydrate, i.e. relevant for the drug release rate into a patient. This is surprisingly the case even if the calcium sulphate hemihydrate has re-crystallized into calcium sulphate dihydrate during the process for preparing the pharmaceutical composition. It is thus important to be able to control the product characteristics of a method for preparing calcium sulphate hemihydrate.
The present invention relates to a process of producing inorganic compositions suitable as carriers for therapeutically active substances to be administered to the human body or any other mammals. The compositions of the invention are based on calcium sulphate and are applicable for several drug delivery purposes; for example, for targeted treatment of specific parts of the body such as diseased organs or for localised treatment of e.g. cancer such as prostate cancer e.g. through targeted and local release of hormonal and anti-hormonal agents.